Methods, systems, and kits for lung volume reduction

ABSTRACT

Lung volume reduction is performed in a minimally invasive manner by isolating a lung tissue segment, optionally reducing gas flow obstructions within the segment, and aspirating the segment to cause the segment to at least partially collapse. Further optionally, external pressure may be applied on the segment to assist in complete collapse. Reduction of gas flow obstructions may be achieved in a variety of ways, including over inflation of the lung, introduction of mucolytic or dilation agents, application of vibrational energy, induction of absorption atelectasis, or the like. Optionally, diagnostic procedures on the isolated lung segment may be performed, typically using the same isolation/access catheter.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods, systems, andkits. More particularly, the present invention relates to methods andapparatus for effecting lung volume reduction by aspirating isolatedsegments of lung tissue.

Chronic obstructive pulmonary disease is a significant medical problemaffecting 16 million people or about 6% of the U.S. population. Specificdiseases in this group include chronic obstructive bronchitis, asthmatic(without bronchitis), and emphysema. While a number of therapeuticinterventions are used and have been proposed, none are completelyeffective, and chronic obstructive pulmonary disease remains the fourthmost common cause of death in the United States. Thus, improved andalternative treatments and therapies would be of significant benefit.

Of particular interest to the present invention, lung function inpatients suffering from chronic obstructive pulmonary disease can beimproved by reducing the effective lung volume, typically by resectingdiseased portions of the lung. Resection of diseased portions of thelungs both promotes expansion of the non-diseased regions of the lungand decreases the portion of inhaled air which goes into the lungs butis unable to transfer oxygen to the blood. Lung reduction isconventionally performed in open chest or thoracoscopic procedures wherethe lung is resected, typically using stapling devices having integralcutting blades.

While effective in many cases, conventional lung reduction surgery issignificantly traumatic to the patient, even when thoracoscopicprocedures are employed. Such procedures often result in theunintentional removal of healthy lung tissue, and frequently leaveperforations or other discontinuities in the lung which result in airleakage from the remaining lung. Even technically successful procedurescan cause respiratory failure, pneumonia, death, and many older orcompromised patients are not even candidates for these procedures. Forthese reasons, it would be desirable to provide improved methods,systems, and kits for performing lung volume reduction which overcome atleast some of the shortcomings noted above.

2. Description of the Background Art

WO 99/01076 describes devices and methods for reducing the size of lungtissue by applying heat energy to shrink collagen in the tissue. In oneembodiment, air may be removed from a bleb in the lung to reduce itssize. Air passages to the bleb may then be sealed, e.g., by heating, tofix the size of the bleb. WO 98/49191 describes a plug-like device forplacement in a lung air passage to isolate a region of lung tissue,where air is not removed from the tissue prior to plugging. WO 98/48706describes the use of surfactants in lung lavage for treating respiratorydistress syndrome.

Patents and applications relating to lung access, diagnosis, andtreatment include U.S. Pat. Nos. 5,752,921; 5,707,352; 5,682,880;5,660,175; 5,653,231; 5,645,519; 5,642,730; 5,598,840; 5,499,625;5,477,851; 5,361,753; 5,331,947; 5,309,903; 5,285,778; 5,146,916;5,143,062; 5,056,529; 4,976,710; 4,955,375; 4,961,738; 4,958,932;4,949,716; 4,896,941; 4,862,874; 4,850,371; 4,846,153; 4,819,664;4,784,133; 4,742,819; 4,716,896; 4,567,882; 4,453,545; 4,468,216;4,327,721; 4,327,720; 4,041,936; 3,913,568 3,866,599; 3,776,222;3,677,262; 3,669,098; 3,498,286; 3,322,126; WO 95/33506, and WO92/10971.

Lung volume reduction surgery is described in many publications,including Becker et al. (1998) Am. J. Respir. Crit. Care Med.157:1593-1599; Criner et al. (1998) Am. J. Respir. Crit. Care Med.157:1578-1585; Kotloffet al. (1998) Chest 113:890-895; and Ojo et al.(1997) Chest 112:1494-1500.

The use of mucolytic agents for clearing lung obstructions is describedin Sclafani (1999) AARC Times, January, 69-97. Use of a balloon-cuffedbronchofiberscope to reinflate a lung segment suffering from refractoryatelectasis is described in Harada et al. (1983) Chest 84:725-728.

SUMMARY OF THE INVENTION

The present invention provides improved methods, systems, and kits forperforming lung volume reduction in patients suffering from chronicobstructive pulmonary disease or other conditions where isolation of alung segment or reduction of lung volume is desired. The methods areminimally invasive with instruments being introduced through the mouth(endotracheally) and/or in some cases through the chest, (e.g.,thoracoscopically), and rely on isolating the target lung tissue segmentfrom other regions of the lung. Isolation is usually achieved byintroducing an isolation/access catheter endotracheally to the airpassages of a lung. By positioning a distal end of an isolation/accesscatheter within an air passage which opens into a target lung tissuesegment, the segment may be isolated by occluding the air passage,typically by inflating an occlusion balloon or other structure on thecatheter within the air passage. The target lung tissue segment may thenbe collapsed by aspirating air (and any other gases or liquids that mayhave been introduced) from the segment, typically through a lumen in theisolation/access catheter. Optionally, the air passage may then besealed, for example by deploying a plug within the air passage. Suitableplugs include swellable collagen matrices which hydrate and expandwithin the air passage so that they fully occlude the passage. Othersealing methods include the use of tissue adhesives, such as fibringlues, cyanoacrylate, etc.; the use of occlusive balloons; the use ofself-expanding meshes, coils, and other occlusive structures; the use ofenergy-induced tissue fusion, such as radiofrequency tissue closure; andthe like.

In a first particular aspect of the methods of the present invention,air flow through and from the target lung tissue segment will beenhanced prior to aspiration of the segment. It is an objective of thepresent invention to aspirate and reduce the volume of the lung tissuesegment as completely as possible. In one instance, obstructions to gasflow within the target tissue segment are reduced prior to or duringaspiration of the segment. Mucus and other obstructions within thetarget lung tissue segment (which is diseased and frequently subject toblockages) will interfere with substantially complete aspiration of thesegment unless removed, disrupted, or otherwise addressed. In a secondinstance, where a lack of lung surfactant is a cause of the impeded airflow, the present invention will provide for administering a suitablesurfactant prior to or during aspiration of the target lung tissuesegment.

In a first specific instance, the present invention reduces gas flowobstructions by inflating the lung tissue segment to a pressure higherthan normal respiratory inflation pressures. Optionally, portions orsegments of the lung adjacent to the target lung segments may bepartially deflated or under-ventilated at the same time that the targetsegment is being inflated at a higher than normal pressure. For example,airflow into adjacent lung segments can be partially blocked to lowerpressure in those segments, causing those segments to partiallycollapse. In a specific instance, a balloon can be used to partiallyblock the bronchus of the lung with the target lung tissue segment.

Usually, the isolated lung tissue segment will be inflated to a pressurein the range from 60 cm H₂O to 200 cm H₂O, preferably in the range from100 cm H₂O to 150 cm H₂O, usually during the administration of generalanesthesia (positive pressure ventilation). If a local anesthesia isbeing used, the pressure will usually be in the range from 10 cm H₂O to100 cm H₂O, preferably from 30 cm H₂O to 60 cm H₂O. The duration of such“over inflation” will typically be in the range from one second to 600seconds, preferably being in the range from 5 seconds to 60 seconds.Such lung inflation may be repeated more than one time. For example, thelung inflation may be carried out by inflating the isolated lung tissuesegment in a pulsatile fashion. Over inflation will usually be performedusing the isolation/access catheter which was used to isolate the lungtissue segment. Optionally, it would be possible to inflate regions ofthe lung percutaneously using a needle introduced through the chest,typically under thoracoscopic observation.

In a second specific instance, gas flow obstructions within the targetlung tissue segment may be reduced by introducing an agent which clearsthe obstructions and/or dilates the air passages to permit gas flowaround any blockages. Exemplary agents include mucolytic agents,bronchodilators, surfactants, desiccants, solvents, necrosing agents,absorbents, and the like. Such agents may be introduced through acatheter, typically through the isolation/access catheter which has beenused to isolate the target lung tissue segment. Optionally, such agentsmay be heated, typically to a temperature in the range from 38° C. to90° C. to enhance activity.

In a third specific instance, gas flow obstructions are reduced bydelivering mechanical energy to the lung segment, typically vibratoryenergy which will break down at least some of the obstructions.Typically, the vibratory energy will be ultrasonic energy, moretypically being ultrasonic energy having a frequency in the range from20 kHz to 20 MHz, usually from 20 kHz to 5 MHz. The mechanical energywill usually be delivered to the target lung tissue segment through anon-compressible fluid introduced to the segment, usually through theisolation/access catheter. It will be appreciated that air is a poortransmission and absorption material for ultrasonic and other vibratoryenergy. Thus, introducing a non-compressible fluid, such as saline,contrast medium, treatment solution (e.g., mucolytic solution,surfactant solution, etc.), or the like, will enhance transmission andabsorption of the energy throughout the target lung tissue segment. Thevibratory energy may then be applied either through a catheter which hasbeen introduced endotracheally and then into the target lung tissuesegment, or externally using a hand-held or other ultrasonic probeintended to deliver ultrasonic energy transcutaneously. Typically, thevibrational treatment will last for time in the range from 5 seconds to60 minutes, usually from 30 seconds to 30 minutes.

In a second aspect of the methods of the present invention, collapse ofthe target isolated lung tissue segment is enhanced by applying externalpressure to the isolated segment. The external pressure will usually beapplied through the chest, e.g., thoracoscopically. Most simply, aneedle can be introduced to a pleural space over the lung, typicallyintracostally (between adjacent ribs). The pleural space can then beinsufflated, e.g., carbon dioxide or other gas inflation mediumintroduced to the pleural space, in order to increase pressure on thelung and enhance collapse of the target segment. Simultaneously, thetarget segment will be aspirated so that the combined lowering of theinternal pressure and raising of the external pressure work tosubstantially completely collapse the segment. Alternatively, theexternal pressure may be applied by inflating a balloon in the pleuralspace over the target lung tissue segment. Still further optionally, theexternal pressure may be applied by a probe which is engaged and pushedagainst at least a portion of the external surface of the lung overlyingthe target segment. Optionally, a thoracoscopically or otherpercutaneously placed needle could be used to puncture and aspirate aportion of the lung, typically in conjunction with a catheter-basedaspiration as described elsewhere herein. For example, portions of thelung which could not be collapsed using an internal catheter could betargeted with an external needle by thoracoscopic visualization. Anypuncture holes left in the lung could then be sealed with a suitableadhesive, such as a fibrin glue.

In a third aspect of the present invention, methods for reducing lungvolume by isolating the lung tissue segment and aspirating the isolatedsegment are combined with diagnostic methods which permit, for example,determination of whether the segment which has been accessed andisolated is in fact diseased and should be collapsed. The diagnosticmethods and steps may take a wide variety of forms. For example, theisolation/access catheter or other endotracheally introduced cathetermay be used to measure air flow to and from the lung tissue segment todetermine whether the air flow capabilities of that segment areimpaired. Alternatively or additionally, the isolation/access cathetermay be used to measure carbon dioxide concentrations within the targetlung tissue segment. Other parameters which may be measured includeforced expiratory volume, pressure, pressure/volume P/V curves, segmentcompliance curves, work of breathing data, perfusion scans,bronchograms, or the like.

In a still further aspect of the methods of the present invention, atarget lung tissue segment is isolated and aspirated, where the segmentis collapsed to a volume which is no greater than 40% of its inflatedsize prior to aspiration, usually being no greater than 30%, andpreferably being no greater than 20%. The inflated size is its maximumsize at normal spontaneous respiratory pressures, assumed to be 40 cmH₂O for patients undergoing positive pressure ventilation, thespontaneous respiratory pressure is assumed to be 90 cm H₂O. The changein volume may be determined by conventional techniques, such asthoracoscopy (X-ray), CT scans, MRI, ultrasound imaging, bronchograms,and the like.

Such efficient collapsing of the target lung tissue segment may beachieved in any of the ways discussed above. Additionally, it may beachieved by inducing absorption atelectasis prior to aspiration. Mostsimply, absorption atelectasis can be induced by insufflating theisolated lung tissue segment with high oxygen concentrations prior toaspiration. The oxygen concentrations in the insufflation gas should beat least 50% by volume, preferably 75% by volume, and more preferablybeing substantially pure oxygen.

The present invention further provides systems for performingintraluminal lung volume reduction procedures according to the methodsof the present invention. The systems comprise at least an isolation oraccess catheter having a proximal end, a distal end, an occlusionelement near the distal end, and at least one lumen therethrough. Theisolation/access catheters are used for establishing access andisolation of a target lung tissue segment, typically by endotrachealintroduction into the air passages of the lung. In a first systemaccording to the present invention, the isolation/access catheter iscombined with a sealing catheter which carries a closure element. Asealing catheter is adapted to be introduced through the lumen of theisolation/access catheter, and the closure element is adapted to bedeployed from the isolation/access catheter within an air passageleading to the target tissue segment. The closure element typicallycomprises a swellable plug, such as a partially hydrated collagen plug.Deployment within the air passage thus permits the plug to swell in situand completely block the air passage leading into the target tissuesegment so that, once the segment is collapsed, air will not enter toreinflate the segment. Surprisingly, it has been found that suchocclusion will substantially inhibit reinflation of the lung, and thatthere is little significant collateral air flow into the collapsedregion.

In a second aspect, the systems of the present invention will combinethe isolation/access catheter with a reagent capable of either clearing,dilating, or widening the air passages in order to facilitatesubstantially complete aspiration of the target tissue segments.Exemplary reagents have been set forth above.

In a third aspect, the systems of the present invention will combine theisolation/access catheter with probes intended for percutaneousintroduction to apply external pressure over the lung. The probes may bein the form of a needle, a balloon, or a simple engagement elementintended for pressing inwardly against the lung.

The present invention still further comprises kits which include atleast an isolation/access catheter as described above. The kits willfurther comprise instructions for use according to any of the methodsset forth above. For example, the instructions for use may set forththat the isolated lung tissue segment is to be over inflated in order toreduce blockages therein. Alternatively, the instructions for use mayset forth that certain agents (as described above) are to be introducedto the segment in order to breakdown obstructive materials prior toaspiration. Still further, the kit instructions may set forth that thelung is to be externally collapsed by applying pressure or otherexternal force to a target tissue segment prior to or simultaneous withaspiration of that segment. Still further, the instructions may setforth that the volume of the target lung tissue segment is to be reducedby at least the percentages set forth above. In all cases, the kits willusually further comprise packaging, such as a pouch, tray, tube, box, orthe like for holding the kit components together with the instructionsfor use. The instructions for use may be printed on a separate sheet(commonly referred to as a package insert) and/or may be printed on thepackaging itself. Usually, the kit components which will be introducedto the patient will be sterilized and packaged in a sterile mannerwithin the kit.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective illustration of an isolation/access catheteruseful in the methods, systems, and kits of the present invention.

FIG. 2 is a cross-sectional view taken along line 2 to a FIG. 1.

FIGS. 3A-3F illustrate alternative cross-sectional views of theisolation/access catheter of FIG. 1.

FIGS. 4A-4C illustrate use of the isolation/access catheter of FIG. 1for isolating and collapsing a target lung tissue segment according theto the methods of the present invention.

FIG. 4D illustrates one protocol for over inflating a target lung tissuesegment prior to aspiration according to the present invention.

FIG. 5 illustrates an optional aspect of the present invention where aninsufflation gas is introduced to aid in the collapse of the targetsegment from the pleural space.

FIG. 6 illustrates an alternative optional aspect of the presentinvention where an inflatable balloon is used to externally collapse aportion of a target lung tissue segment.

FIGS. 7A-7D illustrate alternative balloon designs for use in externalcollapse of the target lung tissue segment.

FIG. 8 illustrates yet another alternative optional aspect of themethods of the present invention where a probe is used to engage andcollapse a portion of a target lung tissue segment.

FIGS. 9A-9C illustrate alternative probe designs.

FIGS. 10A-10C illustrate a sealing catheter carrying a swellable closureelement which may be used in the methods, systems, and kits of thepresent invention.

FIG. 11 illustrates use of the sealing catheter of FIGS. 10A-10C forselectively occluding an air passage leading to a target lung tissuesegment according to the methods of the present invention.

FIGS. 12A-12C illustrate a steerable imaging guidewire which may be usedto facilitate positioning of the isolation/access catheter used in themethods of the present invention.

FIG. 13 illustrates a kit constructed in accordance with the principlesof the present invention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

Lung volume reduction is performed by collapsing a target lung tissuesegment, usually within sub-lobular regions of the lung which receiveair through a single air passage, i.e., segment of the branchingbronchus which deliver to and receive air from the alveolar regions ofthe lung. Such isolated lung tissue segments are first isolated and thencollapsed by aspiration of the air (or other gases or liquids which mayhave been introduced, as discussed below) from the target lung tissuesegment. Lung tissue has a very high percentage of void volume, soremoval of internal gases can reduce the lung tissue to a smallpercentage of the volume which it has when fully inflated, i.e. inflatedat normal inspiratory pressures. The exemplary and preferred percentagesfor the volume reduction are set forth above.

In particular, the present invention provides methods and apparatus forenhancing the aspiration and collapse of the target lung tissue segment.Such methods and apparatus may involve one or more of the followingimprovements. First, various approaches may be taken to remove or lessenobstructions to gas flow within the target tissue region. Second,methods and apparatus may be employed to apply external pressure overthe lung to enhance the collapse achieved by internal aspiration. Third,aspiration of the gases within the target tissue segment may be enhancedby inducing absorption atelectasis prior to aspiration. Absorptionatelectasis may be induced, for example, by introducing an oxygen-richgas to the lung tissue segment, usually at least 50% oxygen by weight,more usually at least 75% oxygen by weight, and preferably substantiallypure oxygen. Absorption atelectasis is a phenomena which occurs when anenriched oxygen mixture is inspired. The high oxygen concentrationcauses an increase in the partial oxygen pressure which in turn causesthe rate of oxygen transfer into the capillary blood within the alveolarregions to increase greatly. The increased oxygen flux may increase somuch that the net flow of gas into the blood exceeds the inspired flowof gas, causing the lung unit to become progressively smaller. Fourth,the access methods and apparatus may be used for performing in situdiagnosis, usually as part of the collapse procedure. Any one of anumber of lung performance characteristics may be measured, typically bysampling using the isolation/access catheter.

The methods of the present invention will generally rely on accessingthe target lung tissue segment using an isolation/access catheteradapted to be introduced endotracheally into the bronchus of the lung.An exemplary isolation/access catheter 10 is illustrated in FIGS. 1 and2 and comprises a catheter body 12 having a distal end 14, a proximalend 16, an inflatable occlusion balloon 18 near its distal end, and atleast one lumen therethrough. Usually, the catheter will have at leasttwo lumens, and catheter 10 includes both a central lumen 20 and anannular lumen 22 defined by inner body member 24 and outer body member26 which is coaxially disposed about the inner body member. The annularlumen 22 opens to port 30 on a proximal hub 32 and provides forinflation of balloon 18. The central lumen 20 opens to port 36 on hub 32and provides for multiple functions, including optional introductionover a guidewire, aspiration, introduction of secondary catheters, suchas sealing catheters, described below, and the like.

The dimensions and materials of isolation/access catheter 10 areselected to permit endotracheal introduction and intraluminaladvancement through the lung bronchus, optionally over a guidewireand/or through a primary tracheal tube structure (as illustrated in FIG.4B below). Suitable materials include low and high densitypolyethylenes, polyamides, nylons, PTFE, PEEK, and the like,particularly for the inner tubular member 24. The outer member,including the occlusion balloon, can be made from elastomeric materials,such as polyurethane, low density polyethylene, polyvinylchloride,silicone rubber, latex, and the like. Optionally, portions of the outertubular member 26 proximal to the inflatable balloon can be made thickerand/or reinforced so that they do not dilate upon pressurization of theballoon. Exemplary dimensions for the isolation/access catheter 10 areset forth in the table below.

ISOLATION/ACCESS CATHETER DIMENSIONS Exemplary Preferred Inner TubularOuter Tubular Inner Tubular Outer Tubular Member Member Member MemberOuter Diameter (mm) 0.4-4   0.6-4.5   1-1.5 2-4 Wall Thickness (mm)0.05-0.25 0.5-0.25 0.1-0.2 0.15-0.25 Length (cm)  50-150 same 50-80 sameBalloon Length (mm) 5-50 10-20 Balloon Diameter (mm) 2-15  6-12(inflated)

The isolation/access catheter 10 may be modified in a number of ways,some of which are illustrated in FIGS. 3A-3F. For example, instead of ainner and outer coaxial tube construction, the catheter can be a singleextrusion having a catheter body 30 with a circular main lumen 32 and acrescent-shaped inflation lumen 34, as illustrated in FIG. 3A.Alternatively, catheter body 40 may be formed as a single extrusionhaving three lumens, i.e., a primary lumen 42 for receiving a guidewire,applying aspiration, and/or delivering secondary catheters. A secondlumen 44 can be provided for inflating the occlusion balloon, and athird lumen 46 can be provided as an alternative guidewire or aspirationlumen. Catheter body 50 comprising a main tubular body 52 having anouter layer 54 fused thereover to define a lumen 56 suitable for ballooninflation as shown in FIG. 3C. A primary lumen 58 is formed within themain tubular member 52. As a slight alternative, catheter body 60 can beformed from a primary tubular member 62, and a secondary tubular member64, where the tubular members are held together by an outer member 66,such as a layer which is applied by heat shrinking. The primary tubularmember 62 provides the main lumen 68 while secondary tube 64 provides asecondary lumen 70. The secondary lumen 70 will typically be used forballoon inflation, while the primary lumen 68 can be used for all otherfunctions of the isolation/access catheter.

Optionally, the isolation/access catheter in the present invention canbe provided with optical imaging capability. As shown in FIG. 3E,catheter body 80 can be formed to include four lumens, typically byconventional extrusion processes. Lumen 82 is suitable for passage overa guidewire. Lumens 84 and 86 both contain light fibers 88 forillumination. Lumen 90 carries an optical wave guide or image fiber 92.Lumen 82 can be used for irrigation and aspiration, typically after theguidewire is withdrawn. Balloon inflation can be effected through thespace remaining and lumens 84 and 86 surrounding the light fibers 88. Asecond catheter body 100 is formed as a coaxial arrangement of a numberseparate tubes. Outer tube 102 contains a separate guidewire tube 104defining lumen 106 which permits introduction over a guidewire as wellas perfusion and aspiration after the guidewire is removed. Second innertubular member 110 will carry an optical image fiber 112 and a pluralityof light fibers 112 are passed within the remaining space 114 within theouter tubular member. In both catheter constructions 80 and 100, forwardimaging can be effected by illuminating through the light fibers anddetecting an image through a lens at the distal end of the catheter. Theimage can be displayed on conventional cathode-ray or other types ofimaging screens. In particular, as described below, forward imagingpermits a user to selectively place the guidewire for advancing thecatheters through a desired route through the branching bronchus.

Referring now to FIG. 4A, a catheter 10 can be advanced to a diseasedregion DR within a lung L through a patient's trachea T. Advancementthrough the trachea T is relatively simple and will optionally employ aguidewire to select the advancement route through the branchingbronchus. As described above, steering can be effected under real timeimaging using the imaging isolation/access catheters illustrated inFIGS. 3E and 3F. Optionally, the isolation/access catheter 10 may beintroduced through a visualizing tracheal tube, such as that describedin U.S. Pat. No. 5,285,778, licensed to the assignee of the presentapplication. The visualizing endotracheal tube 120 includes an occlusioncuff 122 which may be inflated within the trachea just above the branchof the left bronchus and right bronchus LB and RB, respectively. Thevisualizing endotracheal tube 120 includes a forward-viewing opticalsystem, typically including both illumination fibers and an image fiberto permit direct viewing of the main branch between the left bronchus LBand right bronchus RB. Thus, initial placement of isolation/accesscatheter can be made under visualization of the visualizing endotrachealtube 120 and optionally the isolation/access catheter 10 itself.Referring again in particular to FIG. 4A, the isolation/access catheter10 is advanced until its distal end 14 reaches a region in the bronchuswhich leads directly into the diseased region DR. Once in place, theballoon 18 can be inflated and the lung tissue segment which includesthe diseased region isolated from the remainder of the lung. Byisolated, it is meant that air or other gases will not pass between theisolated region and the remaining portions of the lung to anysignificant extent.

As shown in FIG. 4C, it is the object of the present invention to applya vacuum to a lumen within the isolation/access catheter 10 to aspiratethe internal regions within the isolated lung tissue segment in order tocollapse the tissue. This results in a collapsed lung tissue region CLT,as shown as a shaded region in FIG. 4C.

According to the present invention, a variety of steps and protocols maybe performed prior to aspirating the isolated lung tissue region inorder to enhance gas removal from the region. The region may be overinflated, subjected to vibrations, subjected to a dilating or mucolyticagent, or otherwise treated in order to remove gas flow obstructionswithin the region. Each of these methods has been well described aboveand will generally rely on performance of at least one aspect of theprocedure using a lumen of the isolation/access catheter 10. Forexample, over inflation can be effected simply by introducing aninflation gas through the isolation/access catheter to a desiredpressure. Pressure may be measured using a transducer at the distal tipof the catheter 10, but will usually be measured statically at alocation proximal of the catheter. Alternatively or additionally, anoxygen-rich gas can be introduced through the isolation/access catheterin order to induce absorption atelectasis. For vibratory stimulationincompressible fluid may be introduced through the isolation/accesscatheter. Stimulation may be imparted using an external probe and/or avibratory catheter which is introduced through an access lumen of theisolation/access catheter.

As shown in FIG. 4D, in some instances it will be desirable to reduce orselectively control the inflation of the lung tissue adjacent to thetarget lung tissue segment in order to enhance aspiration of the targetsegment. For example, an entire one-half lung can be selectivelycontrolled by an isolation or shunting catheter having a balloon 132near its distal end. The balloon is inflated to occlude a portion of theselected bronchus, typically about 60% of the area. Thus, pressurewithin the lung can be reduced and the lung partly collapsed other thanin the isolated region. In this way, inflation of the target lung tissuesegment can be enhanced which can assist in breaking up occlusionswithin the lung which would otherwise interfere with subsequentaspiration of the segment.

In addition to such in situ techniques for enhancing lung aspiration andcollapse, the present invention can rely on application of an externalforce to assist in collapse. As illustrated in FIG. 5, a needle or othercannula 200 can be percutaneously introduced into a peritoneal space PSbetween the parietal pleural PP and visceral pleural VP. Insufflationgas, such as carbon dioxide, can be introduced through the needle 200,either using a syringe or other pressure source. The gas will typicallybe introduced to a pressure in the range from 30 cm H₂O to 200 cm H₂O inspontaneously breathing patients and 70 cm H₂O to 250 cm H₂O in positivepressure ventilated patients.

Use of an unconstrained insufflation gas, however, is disadvantageoussince it is not directed at a particular target location. In order tomore specifically direct an external pressure against the lung, aballoon 210 can be introduced to the pleural space, typically through athoracic trocar 212. The balloon can be placed based on fluoroscopicobservation. Depending on the particular area which is to be collapsed,a variety of specific balloon configurations can be employed, asillustrated in FIGS. 7A-7D. A generally spherical balloon 220 is shownattached to shaft 220 in FIG. 7A. Other configurations include a wingedprofile (FIG. 7B), a cylindrical or spatula profile (FIG. 7C), and aconvex profile (FIG. 7D). Each of these will be attached to a shaftwhich permits inflation after introduction into the pleural space.

As a further alternative to needle insufflation and balloon expansion, atarget lung tissue segment can be externally collapsed using a simpleprobe 250, usually introduced through a thoracic trocar 252, as shown inFIG. 8. A variety of probes for mechanically engaging and compressingthe outer lung surface are illustrated in FIGS. 9A-9C. Optionally, aneedle can be used to puncture at a desired point in the target tissuelung segment in order to release and/or aspirate air, usually as asupplement to a primary catheter-based aspiration. The puncture can thenbe sealed with fibrin glue or other suitable sealant.

The methods of the present invention will optionally comprise sealing oroccluding the air passage leading to the collapsed tissue region CLT.Such sealing can be performed in a variety of ways, including suturing,gluing, energy-mediated tissue adhesion, and the like. In a preferredaspect of the present invention, a sealing catheter 280 can be used todeliver a plug 282, typically at partially hydrated collagen hydrogel,as illustrated in FIGS. 10A-10C. Usually, the catheter will havedimensions which permit it to be introduced through the main accesslumen of isolation/access catheter 10. The plug 282 will be contained inthe distal tip of a lumen in the catheter, and a push rod 284 extendsthe length of the catheter to permit the treating physician to deploythe plug 282 after the tip of the catheter is properly located, asillustrated in FIG. 11, usually while the balloon on theisolation/access catheter remains inflated and the target lung tissueremains sealed and in an aspirated, collapsed configuration. Oncedeployed within the moist environment of the lung bronchus, the plug 282will absorb water and will swell substantially, typically from 100% to1000% in order to fully occupy and plug the air passage into thecollapsed lung tissue region CLT.

Positioning of the isolation/access catheter 10 within the lung can beperformed using on-board optical imaging capability, as discussed above.Usually, positioning of a guidewire through the branching bronchus willbe manipulated while viewing through the imaging components of theisolation/access catheter. In this way, the isolation/access cathetercan be “inched” along by alternately advancing the guidewire and theisolation/access catheter. As an alternative to providing theisolation/access catheter with imaging, positioning could be done solelyby fluoroscopy. As a further alternative, a steerable, imaging guidewire300 (FIGS. 12A-12C) could be used. The guidewire 300 includes adeflectable tip 302 which can be deflected in a single plane usingpush/pull ribbon 304. Usually, the tip will comprise a spring 306 tofacilitate deflection. In addition to steeribility, the guidewire 300will include an optical imaging wave guide 310 and illuminating opticalfibers 312, as best seen in cross-sectional view of FIG. 12C. Thus, theguidewire 300 can be steered through the branching bronchus to reach thetarget tissue segment using its own in situ imaging capability. Once theguidewire 300 is in place, an isolation/access catheter can beintroduced to the target lung tissue segment as well. Since theguidewire has imaging capability, the isolation/access catheter need notincorporate such imaging. This can be an advantage since it permits theaccess lumen to be made larger since the catheter need not carry anyoptical wave guides.

Referring now to FIG. 13, kits 400 according to the present inventioncomprise at least an isolation/access catheter 10 and instructions foruse IFU. Optionally, the kits may further include any of the othersystem components described above, such as a balloon probe 210, asealing catheter 280, a reagent container 420 (optionally including anyof the dilating or mucolytic agents described above), or othercomponents. The instructions for use IFU will set forth any of themethods as described above, and all kit components will usually bepackaged together in a pouch 450 or other conventional medical devicepackaging. Usually, those kit components, such as isolation/accesscatheter 10, which will be used in performing the procedure on thepatient will be sterilized and maintained sterilely within the kit.Optionally, separate pouches, bags, trays, or other packaging may beprovided within a larger package, where the smaller packs may be openedseparately and separately maintain the components in a sterile fashion.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

What is claimed is:
 1. A method for lung volume reduction, said methodcomprising: isolating a lung tissue segment; reducing gas flowobstructions within the segment; aspirating the segment to cause thesegment to at least partially collapse; and sealing the segment from theremainder of the lung to inhibit reinflation of the lung segment.
 2. Amethod as in claim 1, wherein reducing gas flow obstructions comprisesinflating the lung tissue segment to a pressure higher than its normalinflated pressure.
 3. A method as in claim 2, further comprisingdeflating adjacent lung regions while the lung tissue segment isinflated.
 4. A method as in claim 2, wherein inflating the lung tissuesegment comprises positioning a catheter in an air passage leading intothe segment, inflating a balloon on the catheter to seal the airpassage, and introducing a gas through the catheter to inflate thesegment.
 5. A method as in claim 1, wherein reducing gas flowobstructions comprises introducing an agent to the lung tissue segment,wherein the agent clears or dilates air passages within the segment. 6.A method as in claim 5, wherein the agent is selected from the groupconsisting of mucolytic agents, bronchodilators, surfactants,desiccants, solvents, necrosing agents, and absorbents.
 7. A method asin claim 5, wherein introducing the agent comprises positioning acatheter in an air passage leading to the segment and delivering theagent through the catheter to the segment.
 8. A method as in claim 1,wherein reducing gas flow obstructions comprises delivering mechanicalenergy to the lung segment.
 9. A method as in claim 8, wherein themechanical energy is vibrational energy.
 10. A method as in claim 9,wherein the vibrational energy is delivered by inflating the segmentwith a non-compressible fluid and ultrasonically exciting the fluid todistribute ultrasonic energy throughout the segment.
 11. A method as inclaim 1, wherein isolating the lung tissue segment comprises positioninga catheter in an air passage leading to the lung tissue segment andinflating a balloon on the catheter to occlude the air passage.
 12. Amethod as in claim 11, wherein aspirating comprises drawing gas andliquids present from the isolated lung segment through a lumen in thecatheter while the balloon remains inflated.
 13. A method as in claim11, wherein sealing comprises sealing the air passage which opens to thelung tissue segment to inhibit reinflation of the segment.
 14. A methodas in claim 1, wherein sealing comprises deploying a plug in an airpassage leading to the isolated lung tissue segment.
 15. A method as inclaim 14, wherein the plug is swellable and absorbs water to swellwithin the air passage when deployed.
 16. A method as in claim 15,wherein the plug comprises a collagen hydrogel which is not fullyhydrated prior to deployment.
 17. A method for lung volume reduction,said method comprising: isolating a lung tissue segment; aspirating theisolated segment to cause the segment to collapse, wherein the segmentis collapsed to a volume which is no greater than 40% of the inflatedsize prior to aspiration; and sealing the segment from the remainder ofthe lung to inhibit reinfliction of the lung segment.
 18. A method as inclaim 17, further comprising insufflating the isolated lung tissuesegment with substantially pure oxygen to promote absorption atelectasisprior to aspirating.
 19. A method as in claim 17, wherein isolating thelung tissue segment comprises positioning a catheter in an air passageleading to the lung tissue segment and inflating a balloon on thecatheter to occlude the air passage.
 20. A method as in claim 19,wherein aspirating comprises drawing gas from the isolated lung segmentthrough a lumen in the catheter while the balloon remains inflated. 21.A method as in claim 19, wherein sealing the lung segment comprisessealing the air passage which opens to the lung tissue segment toinhibit reinflation of the segment.
 22. A method as in claim 17, whereinsealing comprises deploying a plug in an air passage leading to theisolated lung tissue segment.
 23. A method as in claim 22, wherein theplug is swellable and absorbs water to swell within the air passage whendeployed.
 24. A method as in claim 23, wherein the plug comprises acollagen hydrogel which is not fully hydrated prior to deployment.
 25. Akit comprising: an isolation/access catheter capable of being introducedtranstracheally into the air passages of the lungs; and instructions tointroduce the isolation/access catheter to a target region of the lungsand to aspirate an isolated tissue segment as follows: isolating a lungtissue segment; reducing gas flow obstructions within the segment;aspirating the segment to at least partially collapse; and sealing thesegment from the remainder of the lung to inhibit reinfection of thelung segment.
 26. A kit as in claim 25, further comprising a sealingcatheter, wherein said instructions further set forth that an airpassage leading to the isolated tissue segment is to be sealed using thesealing catheter after the region has been aspirated.
 27. A kit as inclaim 25, further comprising means for applying external pressure to thelung at the same time the lung is being aspirated.
 28. A kit as in claim25, further comprising an agent which clears or widens air passages inthe lungs when introduced into the lungs prior to aspiration.
 29. A kitas in claim 28, wherein the agent is selected from the group consistingof mucolytic agents, bronchodilators, surfactants, desiccants, solvents,necrosing agents, and absorbents.
 30. A kit comprising: anisolation/access catheter capable of being introduced transtracheallyinto the air passages of the lungs; and instructions to introduce theisolation/access catheter to a target region of the lungs and toaspirate an isolated tissue segment as follows: isolating a lung tissuesegment; aspirating the isolated segment to cause the segment tocollapse to a volume which is no greater than 40% of the inflated sizeprior to aspirating; and sealing the segment from the remainder of thelung to inhibit reinfection of the lung segment.
 31. A kit as in claim30, further comprising a sealing catheter, wherein said instructionsfurther set forth that an air passage leading to the isolated tissuesegment is to be sealed using the sealing catheter after the region hasbeen aspirated.
 32. A kit as in claim 30, further comprising means forapplying external pressure to the lung at the same time the lung isbeing aspirated.
 33. A kit as in claim 30, further comprising an agentwhich clears or widens air passages in the lungs when introduced intothe lungs prior to aspiration.
 34. A kit as in claim 33, wherein theagent is selected from the group consisting of mucolytic agents,bronchodilators, surfactants, desiccants, and solvents.